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Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia.

ABSTRACT: Inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to calicheamicin, is approved in Europe and the United States for treatment of adults with relapsed or refractory acute lymphoblastic leukemia (ALL). Population analyses were performed to evaluate the relationship between InO exposure and efficacy and safety end points in patients with ALL. The probability of achieving complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD)-negativity for InO relative to chemotherapy was also investigated. Data from study 1010 (NCT01363297) and INO-VATE (NCT01564784) were pooled for exposure-response (InO, n = 234) and treatment-response (InO, n = 234; chemotherapy, n = 143) analyses. The analyses demonstrated that InO exposure was significantly correlated with achieving CR/CRi and MRD-negativity, as well as with hepatic event adjudication board-reported veno-occlusive disease/sinusoidal obstruction. Patients with ALL treated with InO had significantly greater odds of achieving CR/CRi (7-times higher) and MRD-negativity (13-times higher) than those receiving chemotherapy.

SUBMITTER: Chen J

PROVIDER: S-EPMC7877846 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia.

Chen Joseph J Haughey May M Vandendries Erik E DeAngelo Daniel J DJ Kantarjian Hagop M HM Ruiz-Garcia Ana A

Clinical and translational science 20200818 1

Inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to calicheamicin, is approved in Europe and the United States for treatment of adults with relapsed or refractory acute lymphoblastic leukemia (ALL). Population analyses were performed to evaluate the relationship between InO exposure and efficacy and safety end points in patients with ALL. The probability of achieving complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual d ...[more]

PMID: 32812370

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Project description:INTRODUCTION:No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies. METHODS:Patient-level data from a study that evaluated InO with standard of care (SoC) chemotherapy (INO-VATE-ALL) and published data from a study that evaluated Blina with SoC chemotherapy (TOWER) were used in the analyses. Endpoints evaluated included remission rate defined as complete remission or complete remission with incomplete hematologic recovery (CR/CRi), hematopoietic stem cell transplantation (HSCT), overall survival (OS), and event-free survival (EFS). For each outcome, treatment-effect modifiers were adjusted for in the anchored MAIC and STC analyses. RESULTS:Analyses showed statistically significant higher rates of remission and HSCT with InO compared to Blina irrespective of the ITC method used or measure of the effect (i.e., odds ratio [OR] or rate difference). The treatment effects derived from the MAIC and STC analyses were consistent and stronger than those estimated from the NMA. A trend favoring InO was detected for EFS. The ITC results for OS suggest no difference between InO and Blina. CONCLUSION:Results from these ITCs indicated a statistically significant advantage for InO over Blina for rates of remission and HSCT in adults with relapsed or refractory B cell precursor ALL. It was not possible to fully adjust for all treatment-effect modifiers, and the similarity in chemotherapy regimens used in the SoC comparator arms of the INO-VATE-ALL and TOWER studies is worthy of further exploration. Both studies, however, used chemotherapy regimens that have a low response rate; therefore, no significant differences in efficacy outcomes are expected between SoC arms. FUNDING:Pfizer Inc, New York, NY. Plain language summary available for this article.

Dataset Information

Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia.

Publications

Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia.

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